Our long-term goal is directed at gaining a more complete understanding of how dependent (T) and thymus independent (B) lymphocytes interact in producing a specific immune response to antigen. More specifically, we feel that the mounting evidence suggesting that T-cells act as regulators of immune responsiveness makes it of particular interest to clarify the nature of the T-cell interaction with antigen. Toward this we plan to focus our immediate attentions on developing methods for the rapid identification and isolation of functional antigen-binding cells. Using enriched populations, we will be better equipped to characterize this subset of T-cells with regard to maturational stage, surface antigenic markers, and relative abilities to participate in other T-dependent functions. In addition it will become possible to follow, biochemically and cytologically, the cellular changes triggered by antigen on reactive T-cells, and to compare these changes in cells from tolerant and immune animals. We feel that the ability to detect, quantify, and isolate specific antigen-binding T-cells will provide a means of analyzing more completely the T-cell-mediated regulatory events that determine whether the response to antigen will be positive (immunity) or negative (tolerance or suppression). Comparative studies of the T-cell's ability to recognize and respond to antigen in normal, immune and tolerant or suppressed animals will be our primary research interest over the period of this grant.